TY - JOUR
T1 - CAC for Risk Stratification Among Individuals With Hypertriglyceridemia Free of Clinical Atherosclerotic Cardiovascular Disease
AU - Cainzos-Achirica, Miguel
AU - Quispe, Renato
AU - Dudum, Ramzi
AU - Greenland, Philip
AU - Lloyd-Jones, Donald
AU - Rana, Jamal S.
AU - Lima, Joao A.C.
AU - Doria de Vasconcellos, Henrique
AU - Joshi, Parag H.
AU - Khera, Amit
AU - Ayers, Colby
AU - Erbel, Raimund
AU - Stang, Andreas
AU - Jöckel, Karl Heinz
AU - Lehmann, Nils
AU - Schramm, Sara
AU - Schmidt, Börge
AU - Toth, Peter P.
AU - Patel, Kershaw V.
AU - Blaha, Michael J.
AU - Bittencourt, Marcio
AU - Nasir, Khurram
N1 - Funding Information:
The Heinz Nixdorf Recall study group is indebted to all of the study participants and to both the dedicated personnel of the study center of the Heinz Nixdorf Recall study and the investigative group, in particular. U. Slomiany, U. Roggenbuck, E.M. Beck, A. Öffner, S. Münkel, R. Peter, and H. Hirche. Advisory Board: T. Meinertz, Hamburg, Germany (Chair); C. Bode, Freiburg, Germany; P.J. deFeyter, Rotterdam, Netherlands; B. Güntert, Halli, Austria; F. Gutzwiller, Bern, Switzerland; H. Heinen, Bonn, Germany; O. Hess, Bern, Switzerland; B. Klein, Essen, Germany; H. Löwel, Neuherberg, Germany; M. Reiser, Munich, Germany; G. Schmidt, Essen, Germany; M. Schwaiger, Munich, Germany; C. Steinmüller, Bonn, Germany; T. Theorell, Stockholm, Sweden; and S.N. Willich, Berlin, Germany. We thank the Heinz Nixdorf Foundation (Chairman: Martin Nixdorf; Past Chairman: Dr Jur Gerhard Schmidty) for their generous support of this study. The authors thank the other investigators, staff, and participants of the MESA study for their valuable contributions. The Multi-Ethnic Study of Atherosclerosis (MESA) was supported by contracts HHSN268201500003I, N01-HC-95159 through N01-HC-95169 from the National Heart, Lung, and Blood Institute (NHLBI) and by grants UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, and UL1-TR-001881 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH). A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. The Coronary Artery Risk Development in Young Adults study (CARDIA) was supported by contracts HHSN268201800003I, HHSN268201800004I, HHSN268201800005I, HHSN268201800006I, and HHSN268201800007I from the National Heart, Lung, and Blood Institute. The DHS was supported in part by grant UL1TR001105 from the NCATS. Parts of the HNR study were also supported by the German Research Council (projects EI 969/2-3, ER 155/6-1;6-2, HO 3314/2-1;2-2;2-3;4-3, INST 58219/32-1, JO 170/8-1, KN 885/3-1, PE 2309/2-1, and SI 236/8-1;9-1;10-1), the German Ministry of Education and Science (projects 01EG0401, 01GI0856, 01GI0860, 01GS0820_WB2-C, 01ER1001D, and 01GI0205), the Ministry of Innovation, Science, Research and Technology, North Rhine-Westphalia, the Else Kröner-Fresenius-Stiftung (project 2015_A119), and the German Social Accident Insurance (DGUV project: FF-FP295). HNR was also supported by the Competence Network for HIV/AIDS, the deanship of the University Hospital and IFORES of the University Duisburg-Essen, the European Union, the German Competence Network Heart Failure, Kulturstiftung Essen, the Protein Research Unit Within Europe, Dr Werner-Jackstädt Stiftung, and the following companies: Celgene München, Imatron/GE-Imatron, Janssen, Merck KG, Philips, ResMed Foundation, Roche Diagnostics, Sarstedt & Co, Siemens HealthCare Diagnostics, and the Volkswagen Foundation. Dr Cainzos-Achirica has received unconditional educational grant to his institution from Amarin Pharmaceuticals. Dr Quispe is supported by an National Institutes of Health (NIH) T32 training grant (5T32HL007227). Dr Joshi has received grants from the American Heart Association (AHA), the National Aeronautics and Space Administration, Novo Nordisk, AstraZeneca, GlaxoSmithKline, Sanofi, Amgen, and Novartis, reports consulting fees from Bayer and Regeneron, and has equity in G3 Therapeutics. Dr Blaha has received research grants from NIH, the Food and Drug Administration, AHA, Amgen Foundation, and Novo Nordisk and is on the advisory boards of Amgen, Sanofi, Regeneron, Novartis, Novo Nordisk, Bayer, Akcea, Kowa, 89Bio, Kaleido, Inozyme, and Roche. Dr Bittencourt has received research grants and speaker fees from GE Healthcare, Bayer, EMS, Boston Scientific, Sanofi, and Novo Nordisk. Dr Nasir is on the advisory boards of Amgen, Novartis, and Novo Nordisk; and his research is partly supported by the Jerold B. Katz Academy of Translational Research. The other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Funding Information:
The Heinz Nixdorf Recall study group is indebted to all of the study participants and to both the dedicated personnel of the study center of the Heinz Nixdorf Recall study and the investigative group, in particular. U. Slomiany, U. Roggenbuck, E.M. Beck, A. Öffner, S. Münkel, R. Peter, and H. Hirche. Advisory Board: T. Meinertz, Hamburg, Germany (Chair); C. Bode, Freiburg, Germany; P.J. deFeyter, Rotterdam, Netherlands; B. Güntert, Halli, Austria; F. Gutzwiller, Bern, Switzerland; H. Heinen, Bonn, Germany; O. Hess, Bern, Switzerland; B. Klein, Essen, Germany; H. Löwel, Neuherberg, Germany; M. Reiser, Munich, Germany; G. Schmidt, Essen, Germany; M. Schwaiger, Munich, Germany; C. Steinmüller, Bonn, Germany; T. Theorell, Stockholm, Sweden; and S.N. Willich, Berlin, Germany. We thank the Heinz Nixdorf Foundation (Chairman: Martin Nixdorf; Past Chairman: Dr Jur Gerhard Schmidty) for their generous support of this study. The authors thank the other investigators, staff, and participants of the MESA study for their valuable contributions.
Publisher Copyright:
© 2022 American College of Cardiology Foundation
PY - 2022/4
Y1 - 2022/4
N2 - Objectives: In this study, we sought to evaluate whether the coronary artery calcium (CAC) score can enhance current paradigms for risk stratification among individuals with hypertriglyceridemia in primary prevention. The eligibility criteria for icosapent ethyl (IPE) were used as case example. Background: Recent trials of atherosclerotic cardiovascular disease (ASCVD) risk-reduction therapies for individuals with hypertriglyceridemia without clinical ASCVD restricted enrollment to participants with diabetes or various other risk factors. These criteria were mirrored in the Food and Drug Administration product label for IPE. Methods: We pooled 2,345 participants with triglycerides 150 to <500 mg/dL (or >178-<500 mg/dL if not on a statin) and without clinical ASCVD from MESA, CARDIA, the Dallas Heart Study, and the Heinz Nixdorf Recall study. We evaluated the incidence of ASCVD events overall, by IPE eligibility (as defined in the product label), and further stratified by CAC scores (0, >0-100, >100). The number needed to treat for 5 years (NNT5) to prevent 1 event was estimated among IPE-eligible participants, assuming a 21.8% relative risk reduction with IPE. In exploratory analyses, the NNT5 was also estimated among noneligible participants. Results: There was marked heterogeneity in CAC burden overall (45% CAC 0; 24% CAC >100) and across IPE eligibility strata. Overall, 17% of participants were eligible for IPE and 11.9% had ASCVD events within 5 years. Among participants eligible for IPE, 38% had CAC >100, and their event rates were markedly higher (15.9% vs 7.2%) and the NNT5 2.2-fold lower (29 vs 64) than those of the 25% eligible participants with CAC 0. Among the 83% participants not eligible for IPE, 20% had CAC >100, and their 5-year incidence of ASCVD (13.9%) was higher than the overall incidence among IPE-eligible participants. Conclusions: CAC can improve current risk stratification and therapy allocation paradigms among individuals with hypertriglyceridemia without clinical ASCVD. Future trials of risk-reduction therapies in hypertriglyceridemia could use CAC >100 to enroll a high-risk study sample, with implications for a larger target population.
AB - Objectives: In this study, we sought to evaluate whether the coronary artery calcium (CAC) score can enhance current paradigms for risk stratification among individuals with hypertriglyceridemia in primary prevention. The eligibility criteria for icosapent ethyl (IPE) were used as case example. Background: Recent trials of atherosclerotic cardiovascular disease (ASCVD) risk-reduction therapies for individuals with hypertriglyceridemia without clinical ASCVD restricted enrollment to participants with diabetes or various other risk factors. These criteria were mirrored in the Food and Drug Administration product label for IPE. Methods: We pooled 2,345 participants with triglycerides 150 to <500 mg/dL (or >178-<500 mg/dL if not on a statin) and without clinical ASCVD from MESA, CARDIA, the Dallas Heart Study, and the Heinz Nixdorf Recall study. We evaluated the incidence of ASCVD events overall, by IPE eligibility (as defined in the product label), and further stratified by CAC scores (0, >0-100, >100). The number needed to treat for 5 years (NNT5) to prevent 1 event was estimated among IPE-eligible participants, assuming a 21.8% relative risk reduction with IPE. In exploratory analyses, the NNT5 was also estimated among noneligible participants. Results: There was marked heterogeneity in CAC burden overall (45% CAC 0; 24% CAC >100) and across IPE eligibility strata. Overall, 17% of participants were eligible for IPE and 11.9% had ASCVD events within 5 years. Among participants eligible for IPE, 38% had CAC >100, and their event rates were markedly higher (15.9% vs 7.2%) and the NNT5 2.2-fold lower (29 vs 64) than those of the 25% eligible participants with CAC 0. Among the 83% participants not eligible for IPE, 20% had CAC >100, and their 5-year incidence of ASCVD (13.9%) was higher than the overall incidence among IPE-eligible participants. Conclusions: CAC can improve current risk stratification and therapy allocation paradigms among individuals with hypertriglyceridemia without clinical ASCVD. Future trials of risk-reduction therapies in hypertriglyceridemia could use CAC >100 to enroll a high-risk study sample, with implications for a larger target population.
KW - cardiovascular disease
KW - coronary artery calcium
KW - hypertriglyceridemia
KW - icosapent ethyl
KW - prevention
KW - primary prevention
KW - risk
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U2 - 10.1016/j.jcmg.2021.10.017
DO - 10.1016/j.jcmg.2021.10.017
M3 - Article
C2 - 34922873
AN - SCOPUS:85122967092
SN - 1936-878X
VL - 15
SP - 641
EP - 651
JO - JACC: Cardiovascular Imaging
JF - JACC: Cardiovascular Imaging
IS - 4
ER -
